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Biomedical subjects

E N Myers

Publications and source records attributed to E N Myers.

At least 19 recordsLinked to original sources

Loss of heterozygosity of the short arm of chromosomes 3 and 9 in oral cancer.

Loss of heterozygosity (LOH) on chromosomes 3p and 9p has been documented in a variety of malignancies, which suggests the presence of tumor suppressor gene loci on these chromosomes. We have studied 77 oral carcinomas for LOH using 16 microsatellite markers distributed over 5 human chromosomes. Fifty-five (71%) of these tumors showed LOH at one or more loci. A significant proportion of LOH at the informative tumors was observed at chromosomes 3p and 9p: 58% and 48%, respectively. A majority of the tumors showed losses at multiple loci on chromosomes 3p or 9p or on both. Our results suggest that tumor suppressor genes located on the short arms of chromosomes 3 and 9 may be involved in the pathogenesis of oral carcinoma. These regions of deletion observed in oral cancers overlap those reported in other neoplasms. However, we did not find any evidence of these changes in tumor margins with early pathological changes.

Carcinoma, Squamous Cell

A long-term assessment of adjuvant chemotherapy on outcome of patients with extracapsular spread of cervical metastases from squamous carcinoma of the head and neck.

BACKGROUND: Extracapsular spread (ECS) of cervical lymph node metastases of squamous cell carcinoma from head and neck sites portend poor prognosis. Therefore, a program of combined surgery, postoperative irradiation therapy, and adjuvant methotrexate and 5-fluorouracil (5-FU) was initiated in 1982 for such patients. METHOD: All patients operated on between June 1982 and December 1992 by the full-time faculty of the Department of Otolaryngology at the University of Pittsburgh School of Medicine were eligible and reported in this trial. All patients had negative surgical margins of excision of the primary carcinoma, and histologic evidence of cervical metastases with ECS. Postoperative irradiation included 50-60 cGy for 5 to 6 weeks followed by methotrexate and 5-FU administered on an outpatient basis on days 1 and 8 every 21 days. All patients were followed for 30 or more months for evidence of recurrent disease. RESULT: A total of 371 patients met eligibility criteria. Of this group, 53 (14%) were treated with surgery only, 187 (50%) received surgery and postoperative irradiation, and 131 (35%) received surgery, irradiation therapy, and chemotherapy. The primary site, extent of nodal involvement, and stage of the three patient groups were similar. However, performance status (Karnofsky) was best in the patients who received chemoradiation (average 90) when compared with those who received surgery and irradiation (average 80) or surgery only (average 70). Absolute disease free survival rate (30 months) was 9.5% in patients treated with surgery only, 34% in patients treated with surgery plus irradiation, and 53% in patients treated with surgery, irradiation, and chemotherapy. When adjusted for patients who died of intercurrent disease with less than 30 months follow-up, survival rates became 17%, 40%, and 58%, respectively. These differences are highly significant (P < 0.001). CONCLUSION: Results of this study suggest that postoperative chemoradiation may improve survival in patients with ECS of cervical metastases. Compliance with the chemoradiation was suboptimal and suggests that improved strategy must be developed.

Aged

Malignant melanoma metastatic to the tonsil.

Metastasis to the oral cavity from melanoma arising in distant sites is very rare. The authors present three cases of melanoma metastatic to the palatine tonsil: two were cutaneous melanomas and one arose from the mucous membrane of the hard palate. Fewer than 30 cases of metastatic melanoma to the palatine tonsil have been reported, and none have been from mucosal melanoma originating from another mucosal primary site in the head and neck. From this perspective, one of the cases in this article is unique. The authors present clinical histories of the three cases of melanoma metastatic to the palatine tonsil. Two patients were still alive a substantial time after treatment. The case presentations indicate that careful examination of the head and neck should be part of the routine follow-up examination in all melanoma patients.

Adult

Management of carcinoma of the supraglottic larynx: evolution, current concepts, and future trends.

The treatment of cancer of the supraglottic larynx has undergone an evolution. Better understanding of the anatomy and biology of cancer in this anatomic site has enabled surgeons to devise effective oncologic strategies while making every effort to preserve the function of the larynx. Certain recent concepts and changing trends have emerged in the treatment of cancer of the supraglottic larynx, including the treatment of the neck, significance of extracapsular spread of tumor in cervical lymph nodes, and conservation laser surgery. In 1985, Snyderman et al. reported the prognostic significance of extracapsular spread in patients with cancer of the supraglottic larynx. In 1990, Lutz et al. reported the results of our experience with the treatment of 202 patients. The review verified the significant risk of bilateral neck disease in these patients, even with adjuvant radiation therapy. Accordingly, since 1990 all patients having cancer of the supraglottic larynx have been treated in the Department of Otolaryngology at the University of Pittsburgh with bilateral neck dissections. The use of adjuvant radiation therapy has been based on the presence of extracapsular spread. This study documents the oncologic effectiveness of this treatment and confirms the efficacy of bilateral neck dissections in an attempt to control neck disease and the prognostic significance of extracapsular spread. We review the evolution of the treatment of cancer of the supraglottic larynx, present our results, and consider innovative surgical approaches.

Adult

Microsatellite instability in oral cancer.

Generalized genomic instability, detected as somatic changes in allele sizes at microsatellite loci in tumors compared to peripheral lymphocyte DNA, is a recently recognized mechanism of mutation in cancer. Such instability results from the somatic loss of DNA mismatch repair capability. Germ-line mutations at DNA mismatch repair loci confer susceptibility to colon cancer in hereditary non-polyposis colorectal cancer. Somatic loss of DNA mismatch repair has been reported in a large variety of other tumor types. Our goal was to determine the frequency of microsatellite instability in a large series of oral tumors. Out of 91 tumors analyzed for microsatellite instability, 6 (7%) showed microsatellite instability. Instability was observed at multiple loci with a range of 50-74% of loci affected. Alterations include both increase (74%) and decrease (26%) in allele sizes. The proportion of alleles affected ranged from 30-58% of all alleles. Our data suggest that somatic genomic instability plays a role in the pathogenesis of a small subset of oral tumors.

Adult

T3 glottic carcinoma revisited. Transglottic vs pure glottic carcinoma.

OBJECTIVE: To compare results of treatment of patients who have T3 transglottic carcinoma with patients who have T3 pure glottic carcinoma. DESIGN: A retrospective cohort study from January 1976 to December 1990 with a minimum 2-year follow-up. SETTING: Eye and Ear Hospital, University of Pittsburgh Medical Center. PATIENTS: The medical records of 161 patients with T3 glottic carcinoma were reviewed. We excluded 17 patients who were unavailable for follow-up or who had died of other causes but were free of glottic carcinoma. Therefore, 144 patients were entered into this study--79 patients with transglottic carcinoma and 65 with pure glottic carcinoma. INTERVENTION: Three treatment groups consisted of the following: 30 patients in whom a full course of radiation therapy failed and who subsequently underwent salvage surgery; 92 patients who underwent surgery only; and 22 patients who underwent surgery and had postoperative radiation therapy. Seventy-five patients had total laryngectomy, and 69 had total laryngectomy with neck dissection. MAIN OUTCOME MEASURES: Cervical metastasis, extracapsular spread, local failure, stomal recurrence, distant metastasis, and 2 years with no evidence of disease. RESULTS: Patients with T3 transglottic carcinoma had a higher incidence of occult cervical metastasis (12% vs 9%), overall cervical metastasis (27% vs 17%), and extracapsular spread (43% vs 27%) than did patients with T3 pure glottic carcinoma. Two years of no disease was similar in these two groups (80% vs 79%). Extracapsular spread had a notable effect on distant metastasis and on 2 years of no disease. CONCLUSION: Patients with T3 transglottic carcinoma had a higher incidence of cervical metastasis and extracapsular spread than patients with T3 pure glottic carcinoma. Every patient with T3 transglottic carcinoma should be treated with total laryngectomy with neck dissection.

Adult

Floor of mouth carcinoma. The management of the clinically negative neck.

OBJECTIVES: Examine the management of the clinically negative neck and evaluate the role of elective neck dissection in patients with squamous carcinoma of the floor of the mouth. DESIGN: Retrospective analysis of a cohort of patients with squamous carcinoma of the floor of the mouth and N0 stage disease of the neck who were treated between 1973 and 1992. The mean follow-up was 6 years. PATIENTS: The cohort consisted of 129 patients. Excluded from analysis were patients without evidence of disease but less than 3 years of follow-up and those with uncertain resection margins. INTERVENTION: Resection of the floor of the mouth lesion with or without marginal mandibulectomy. Elective lymphadenectomy was performed in 26 (23%) of the 129 patients. OUTCOME MEASURE: Estimates were obtained of survival according to mode of therapy, classification of treatment modality, determinate cure, locoregional failure, salvage, and occult disease by clinical stage. RESULTS: Occult disease was detected in 23% of the patients who underwent elective neck dissection. Recurrence in the neck occurred in 36% of 103 patients who received follow-up but did not undergo elective neck dissection. The determinate survival at 3 years was 100% for patients with occult disease who underwent elective neck dissection. Overall, 96% of the patients who were treated with elective neck dissection were cured; 85% of the patients who received no initial treatment of the neck were cured; and 59% of the patients with failure in the neck were salvaged. CONCLUSIONS: A more aggressive approach to the neck with N0 disease may be warranted. Selective neck dissection allows early removal of occult metastases with acceptable morbidity. In elective dissection for clinically and histologically negative necks, the high rate of survival may result from the removal of metastatic carcinoma that was missed in the histopathologic sampling process.

Adult

Visualization of INT2 and HST1 amplification in oral squamous cell carcinomas.

Oral squamous cell carcinoma (OSCC) develops along a multistep genetic pathway including loss of tumor suppressor genes and alteration of oncogenes. We characterized seven OSCC cell lines by classical and molecular cytogenetic analysis and fresh tumor and adjacent oral mucosa corresponding to three of the cell lines by molecular cytogenetics. We observed homogeneously staining regions (hsrs) in four of the seven cell lines, at 11q13 in three and at 11q23 and in an unidentified marker chromosome in the fourth. Amplification of band 11q13 occurs in 30-60% of head and neck squamous cell carcinomas. To determine whether INT2 and HST1, both located in band 11q13, are amplified in the tissues and cell lines and to confirm the chromosomal location(s) of the amplification, we used dual-color fluorescence in situ hybridization (FISH) with DNA probes for these genes and the chromosome 11 centromere. We report chromosomal localization of INT2/HST1 amplification in OSCC. Coamplification of INT2 and HST1 was detected in the hsrs in cultured tumor cells from the four hsr-containing tumors and in directly harvested tumor cells, which were available from only two of these tumors. Amplification was not present in tumors lacking hsrs or adjacent oral mucosa corresponding to any of the seven tumors. The observation of amplification in fresh tumor cells suggests that the amplification was present in the patients, may play a key role in the development and/or progression of OSCC, and is not due to karyotypic evolution in vitro. The absence of amplification in the adjacent mucosa suggests that 11q13 amplification is a relatively late event in OSCC tumorigenesis.

Biopsy

Accuracy of intraoperative staging of the NO neck in squamous cell carcinoma.

Management of the neck in squamous cell carcinoma of the upper aerodigestive tract continues to be a topic of great debate. One major problem is that incorrect clinical staging is expected in approximately 20% of necks. This is true of both clinical stage NO and N+ necks, even when imaging studies are used. This prospective study of 108 necks in 79 patients examined the role of intraoperative palpation and inspection in improving the surgeon's ability to predict nodal stage. Of 62 patients with NO necks clinically on both sides, 26 were staged N+ by intraoperative node examination. Nineteen of the 26 were histologically negative (73% false-positive). Of the 36 patients staged intraoperatively as NO, 10 were histologically positive (28% false-negative). Of 108 necks judged clinically to be NO, 25 (23%) had occult metastases and 11 (10%) had extracapsular spread. Forty-one of 108 clinical NO necks were believed to have positive nodes at the time of neck dissection. Of these 41 necks, 30 (73%) were found to be histologically NO (false-positive). Of the 67 clinical NO necks that were also believed to be NO intraoperatively, occult metastases were found in 14 (21% false-negative). Therefore, intraoperative staging did not significantly improve the false-negative rate. Frozen-section biopsy obtained in the operating room was reliable in 24 (92.3%) of 26 patients. Although frozen-section biopsy was not performed in all patients, these data suggest that upstaging the neck without frozen-section biopsy is much less reliable. This study supports the use of frozen-section biopsy before converting the selective dissection to a radical or modified neck dissection in most instances.

Biopsy

The impact of bilateral neck dissection on pattern of recurrence and survival in supraglottic carcinoma.

OBJECTIVE: The findings of an initial evaluation of 202 patients treated for squamous cell carcinoma of the supraglottic larynx have been previously reported. Recurrent disease was observed at the primary site in four patients (2%), in the regional lymphatics in 39 patients (20%), and at distant sites in 24 patients (12%). Critical analysis of patients who demonstrated recurrent disease in the cervical lymphatics indicated that 38 of 39 recurrences developed in nonsurgically treated necks irrespective of the use of postoperative radiation therapy. Accordingly, all patients with supraglottic carcinoma have been treated with routine bilateral neck dissection since that time. We have reviewed our data to determine if bilateral neck dissections deter recurrence and improves survival. DESIGN: A retrospective review of the clinical course of 76 patients undergoing excision of supraglottic squamous carcinoma combined with bilateral neck dissection between 1980 and 1990 was performed to determine survival and recurrence rates. Surgery alone was used to treat 32 patients, while 44 patients were treated with surgery plus adjunctive therapy. SETTING: Department of Otolaryngology--Head and Neck Surgery, The Eye and Ear Institute, University of Pittsburgh (Pa) School of Medicine. RESULTS: Distant metastatic spread was the most frequent site of failure, occurring in nine (11.8%) of 76 patients. Local recurrence was experienced by two patients (1%). The incidence of cervical recurrence (seven patients, 9.2%) following treatment for squamous cell carcinoma of the supraglottic larynx has been reduced from 20% to 9% through the use of bilateral neck dissection. The 2-year survival rate increased from 72% to 76%. CONCLUSION: Routine bilateral neck dissection is beneficial in the surgical management of squamous cell carcinoma of the supraglottic larynx.

Adult

Phase Ib trial of the effect of peritumoral and intranodal injections of interleukin-2 in patients with advanced squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology Group trial.

Thirty-six patients with unresectable squamous cell carcinoma of the head and neck were entered into a phase Ib trial evaluating the toxicity, maximally tolerated dose (MTD), and immunomodulating effects of locally administered interleukin-2 (IL-2). Patients received daily IL-2 injected perilesionally in divided doses in each of four quadrants and bilaterally into the superior jugular lymph nodes. The dose of IL-2 began at 200 U/day and was escalated to 4 x 10(6) U/day in groups of six patients. Overall, regionally administered IL-2 was well tolerated. The most frequently encountered toxicities were fever, hepatotoxicity, and hypotension. Dose-limiting toxicity was encountered at 4 x 10(6) U. Of the 36 patients treated, 2 partial responses were noted at 2,000 and 4 x 10(6) U. We conclude that regionally administered IL-2 is well tolerated in patients with head and neck cancer and that the MTD is 2 x 10(6) U/day, similar to what has been reported with systemically administered IL-2. Although the overall response rate was low, it may be improved with prolonged administration of IL-2 or by combining it with other biologic or cytotoxic agents.

Adult

Microlaryngoscopic surgery for T1 glottic lesions: a cost-effective option.

Excision of squamous cell carcinoma of the vocal cord using microlaryngoscopy (ML) with or without laser is a cost-effective treatment option in highly selected patients. A retrospective review of 50 cases of invasive and microinvasive squamous cell carcinoma demonstrated a failure rate of 8% (4 patients), all of whom were successfully salvaged by hemilaryngectomy (1 patient) or irradiation (3 patients). Other treatment options for T1 glottic lesions include hemilaryngectomy or radiotherapy, yielding similar cure rates of 95% and 67% to 93%, respectively. Investigation of the potential savings by extrapolating 1992 health care costs into the treatment options for T1 glottic carcinoma resulted in costs of $12,956 per patient for ML, while hemilaryngectomy averaged $35,616 per patient and radiotherapy netted costs of $32,588 per patient. Extrapolating these costs to a theoretic group of 100 patients, ML provided savings of 2.4 million dollars when compared to the other treatment modalities. In selected patients, ML for T1 glottic cancer provides an effective therapeutic modality suited to our cost-conscious environment.

Adult

Glomus vagale: paraganglioma of the vagus nerve.

Review of the experience of a single institution with a rare tumor may give inadequate and biased information. In an effort to better understand issues related to diagnosis and subsequent management of paraganglioma of the vagus nerve, review of the experience at two university medical centers was undertaken. A review of the records of all patients with a diagnosis of vagal paraganglioma at the University of Pittsburgh and the Eastern Virginia Medical School was undertaken. Presenting signs and symptoms, treatment, and subsequent outcome were assessed. Data on 19 patients with vagal paraganglioma were available. The most common initial finding was a neck mass. Forty-seven percent (9/19) had vocal cord paralysis at presentation. Angiography was beneficial in helping to make the diagnosis and in identifying synchronous tumors. History of familial paraganglioma was present in 47% (9/19). Multiple paragangliomas were diagnosed in 53% (10/19) cases in our study. Of the patients with familial vagal paraganglioma, 89% (8/9) had multiple paraganglioma. All patients treated with surgery had postoperative vocal cord paralysis. Elective management of patients with bilateral vagal paraganglioma is a special dilemma. Radiation therapy of selected "operable" patients may be indicated because of the potential for bilateral vocal cord paralysis in these patients and its attendant sequela.

Adult

Malignant neoplasms of the hard palate and upper alveolar ridge.

Malignant neoplasms of the hard palate and upper alveolar ridge can arise from the epithelial (mucosal), salivary, hematopoietic, or mesenchymal tissues in this region. Unlike other regions in the head and neck, only about two thirds of malignant neoplasms of the hard palate are squamous cell carcinomas, and few large series have reported treatment protocols and outcomes for patients with these tumors. In this review, we will describe our series of 51 patients with malignant neoplasms of the hard palate and upper alveolar ridge. This review will emphasize the surgical treatment program and rehabilitative techniques developed at the University of Pittsburgh.

Alveolar Process